Most epidemiological studies on cardiovascular disease have concentrated on long-term exposures that contribute to the onset of disease years to decades later. A more recent area of research has, however, focused on the short-term events that trigger the onset of an acute myocardial infarction. It has been shown that heavy physical exertion and coffee intake are two triggers of acute myocardial infarction. However, it is possible that genetic variation alter the susceptibility to the acute effects of heavy physical exertion and coffee. We will use the unique characteristics of the case-crossover study to assess potential effect modification by genetic variation on the triggering of myocardial infarction by coffee intake and heavy physical exertion. The case-crossover design is a method for studying transient effects on the risk of acute events. Rather than comparing some individuals with others, as would a usual case-control design, we make comparisons within individuals, comparing the hazard period (time period right before the event) with a control period. Therefore, any fixed (i.e. not time-varying) characteristics like age, sex, genetic background, etc. cannot be assessed as main effects. However, fixed characteristics can be evaluated as modifiers of the transient exposure. Our overall objective is to identify genetic modifiers of triggers of acute myocardial infarction by examining genes involved in the sympathetic nervous system, renin-angiotensin system, caffeine metabolism, and genes that mediate some of the physiologic effects of caffeine. We will also evaluate 21 polymorphisms identified in recent genome-wide association studies. The study population consists of 2,300 incident cases of nonfatal myocardial infarction in the Central Valley of Costa Rica recruited from 1994 to 2004. DNA is already available in this population. The proposed study is novel and offers an unusual opportunity to expand our understanding of how genetic background can modify the triggering effect of transient risk exposures. Understanding the genetic basis for the variability in response to triggers of myocardial infarction is essential for identifying susceptible sub-populations that can modify their life styles to improve health. PUBLIC HEALTH RELEVANCE: This study will help understand the genetic basis for the variability in response to triggers of myocardial infarction. Results from this study may help to identify susceptible sub-populations that can modify their life styles to improve health.